Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function?

During the last few years, an increased interest in the possibility of immune mediated pathophysiology of obsessive compulsive disorder (OCD) and related disorders has been seen. In the late 1980s, the National Institute of Mental Health reported an increase of obsessive compulsive symptoms in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCD symptoms but no chorea led to the coining of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). This association has furthered interest in studying immune parameters in non-PANDAS OCD as well. This article will review the neuropsychiatric findings in OCD and Tourette syndrome (TS) with emphasis placed on PANDAS, and its association with SC, and a review of the existing studies that have assessed immunologic measures in patients with OCD and TS.

Intensive remedial instruction for children with severe reading disabilities: immediate and long-term outcomes from two instructional approaches.

Sixty children with severe reading disabilities were randomly assigned to two instructional programs that incorporated principles of effective instruction but differed in depth and extent of instruction in phonemic awareness and phonemic decoding skills. All children received 67.5 hours of one-to-one instruction in two 50-minute sessions per day for 8 weeks. Both instructional programs produced very large improvements in generalized reading skills that were stable over a 2-year follow-up period. When compared to the growth in broad reading ability that the participants made during their previous 16 months in learning disabilities resource rooms, their growth during the intervention produced effect sizes of 4.4 for one of the interventions and 3.9 for the other. Although the children's average scores on reading accuracy and comprehension were in the average range at the end of the follow-up period, measures of reading rate showed continued severe impairment for most of the children. Within 1 year following the intervention, 40% of the children were found to be no longer in need of special education services. The two methods of instruction were not differentially effective for children who entered the study with different levels of phonological ability, and the best overall predictors of long-term growth were resource room teacher ratings of attention/behavior, general verbal ability, and prior levels of component reading skills.

A family with a grand-maternally derived interstitial duplication of proximal 15q.

About 1% of individuals with autism or types of pervasive developmental disorder have a duplication of the 15q11-q13 region. These abnormalities can be detected by routine G-banded chromosome study, showing an extra marker chromosome, or demonstrated by fluorescence in situ hybridization (FISH) analysis, revealing an interstitial duplication. We report here the molecular, cytogenetic, clinical and neuropsychiatric evaluations of a family in whom 3 of 4 siblings inherited an interstitial duplication of 15q11-q13. This duplication was inherited from their mother who also had a maternally derived duplication. Affected family members had apraxia of speech, phonological awareness deficits, developmental language disorder, dyslexia, as well as limb apraxia but did not have any dysmorphic clinical features. The observations in this family suggest that the phenotypic manifestations of proximal 15q duplications may also involve language-based learning disabilities.

On defining Sydenham's chorea: where do we draw the line?

Sydenham's chorea (SC) is a major manifestation of rheumatic fever characterized by an array of neuropsychiatric symptoms that vary in severity, timing, and character. Some of the same symptoms are seen in Tourette's syndrome and childhood-onset obsessive-compulsive disorder. Genetic vulnerability appears to play a role in all three conditions. The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) has been introduced to describe a putative subset of obsessive-compulsive disorder and Tourette's syndrome that bears some resemblance to Sydenham's chorea. This article discusses whether PANDAS should be subsumed under Sydenham's chorea, thus expanding the diagnostic boundaries of Sydenham's chorea to include primarily neuropsychiatric presentations now classified as cases of obsessive-compulsive disorder or Tourette's syndrome. We conclude that PANDAS is a useful construct, but that it would be premature to view it as a subset of Sydenham's chorea-whether defined narrowly or broadly.

XLMR syndrome characterized by multiple respiratory infections, hypertelorism, severe CNS deterioration and early death localizes to distal Xq28.

We report on a family with severe X-linked mental retardation (XLMR) and progressive, severe central nervous system deterioration. Three of the five affected males died of secondary complications before the age of 10 years and none have survived past the age of 10. These complications included swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections. In addition, hypotonia and a mild myopathy were also present. All had a characteristic facies, including downslanting palpebral fissures, hypertelorism, and a short nose with a low nasal bridge. The two older boys showed cerebral atrophy by CT. No metabolic abnormalities were identified. Three obligate carriers had an IQ less than 80. The causal gene has been localized distal to DXS8103 in Xq28, a region spanning 5cM. No other XLMR disorder with these manifestations have been localized to this region and this appears to be a new disorder.

Developmental dyslexia: a motor-articulatory feedback hypothesis.

Reading is mediated by parallel and widely distributed modular systems. There are, therefore, multiple loci in these systems where dysfunction may lead to developmental dyslexia. However, most normal children learn to read using the alphabetic system. Learning to use this system requires awareness that words are comprised of a system of speech sounds (phonological awareness) and the knowledge of how to convert letters (graphemes) into these speech sounds (phonemes). Most dyslexic children have deficient phonological awareness and have difficulty converting graphemes into phonemes. Studies of patients with acquired lesions who are unable to convert graph-emes into phonemes, as well as positron emission tomographic studies of normal subjects, suggest that the left inferior frontal lobe is important in phonologic reading. Phonetic gestures are represented in the brain as invariant motor commands that program the articulators. Phonologic reading may activate the left inferior frontal lobe because grapheme-to-phoneme conversion requires activation of these motor-articulatory gestures. Dyslexic children are unaware of the position of their articulators during speech. The inability to associate the position of their articulators with speech sounds may impair the development of phonological awareness and the ability to convert graphemes to phonemes. Unawareness of their articulators may be related to programming or feedback deficits.

Attention deficit-hyperactivity disorder and asymmetry of the caudate nucleus.

The neurologic basis of attention deficit-hyperactivity disorder (ADHD) is poorly understood. Based on previous studies that have implicated metabolic deficiencies in the caudate-striatal region in ADHD, we employed magnetic resonance imaging to investigate patterns of morphology of the head of the caudate nucleus in normal and ADHD children. In normal children, 72.7% evidenced a left-larger-than-right (L > R) pattern of asymmetry, whereas 63.6% of the ADHD children had the reverse (L < R) pattern of asymmetry of the head of the caudate nucleus. This reversal of normal asymmetry in ADHD children was due to a significantly smaller left caudate nucleus. The reversal in asymmetry of the head of the caudate was most notable in ADHD males. These results suggest that normal (L > R) morphologic asymmetry in the region of the caudate nucleus may be related to asymmetries observed in neurotransmitter systems implicated in ADHD. The behavioral symptoms of ADHD may reflect disinhibition from normal levels of dominant hemispheric control, possibly correlated with deviations in asymmetric caudate-striatal morphology and deficiencies in associated neurotransmitter systems.

Anomalous cerebral structure in dyslexia revealed with magnetic resonance imaging.

OBJECTIVE: To develop quantitative methods for identifying cerebral anomalies on magnetic resonance images of subjects with language disorders and other learning disabilities. DESIGN: Partially blinded comparison of subjects with dyslexia, unaffected relatives, and a control group balanced for age and socioeconomic status. Criterion standard: clinical diagnosis of dyslexia by physician or learning disabilities specialist on the basis of clinical assessment and family history. SETTINGS: Hospital pediatric neurology clinic and private reading clinic. VOLUNTEERS: individuals with dyslexia (seven male and two female, aged 15 to 65 years) from professional families; unaffected first- and second-degree relatives (four male and six female, aged 6 to 63 years) available in the geographical area; and controls (five male and seven female, aged 14 to 52 years). INTERVENTIONS: Gradient echo three-dimensional scan in Seimens 1-Tesla Magnetom; 128 1.25-mm consecutive sagittal images. MAIN OUTCOME MEASURES: (1) Average length of the temporal (T) and parietal (P) banks of the planum temporale; (2) interhemispheric coefficients of asymmetry for T and P banks: Left-Right interhemispheric coefficients of asymmetry = (L-R)/[(L+R)/2]; (3) intrahemispheric coefficients of asymmetry = (T-P)/[(T+P)/2]; and (4) qualitative assessment of gyral variants in the parietotemporal operculum. RESULTS: All groups had left-sided asymmetry for the temporal bank and right-sided asymmetry for the parietal bank. The group with dyslexia had exaggerated asymmetries, owing to a significant shift of right planar tissue from the temporal to parietal bank. They also had a higher incidence of cerebral anomalies bilaterally (subjects with dyslexia, six of nine; relatives, two of 10; and controls, zero of 12). CONCLUSIONS: Quantitative assessment of high-resolution magnetic resonance images can reveal functionally relevant variations and anomalies in cerebral structure. Further refinement of these measurement techniques should improve the diagnosis, classification, and treatment of language disorders and other learning disabilities.

Angelman and Prader-Willi syndrome: a magnetic resonance imaging study of differences in cerebral structure.

Recent improvements in magnetic resonance imaging techniques now allow the developing brain to be visualized in sufficient detail to perform "in vivo neuropathology." In this study we compared the cortical morphology in six children with Angelman and four with Prader-Willi syndrome. These two syndromes are of special interest because, although they are both caused by deletions in the same region of chromosome 15, Angelman children are far more severely affected, and do not speak. We measured the length of the banks of the Sylvian fissure in a gapless series of thin sagittal images. Angelman children had a significantly larger proportion (75%) of anomalous fissures than the Prader-Willi children (12%). Anomalous cortical growth could result from mistimed expression and recognition of macromolecules involved in axonal guidance, target recognition, and pruning. We hypothesize that misrouting of long projection axons may be related to the Sylvian fissure anomalies and the language disorder in Angelman syndrome.

A possible pathophysiologic substrate of attention deficit hyperactivity disorder.

The attention deficit hyperactivity disorder (ADHD) is associated with defective attention and response inhibition and motor restlessness. Inattention, defective response inhibition, and impersistence are more commonly seen in adults with right than with left hemisphere dysfunction. In light of this fact and because children with ADHD not only appear to demonstrate these symptoms but also neglect the left side and have decreased activation of their right neostriatum, we propose that these children have a right hemisphere dysfunction. In addition, because both inattention and defective response inhibition can be seen in children with ADHD and in patients and animals who have frontal lobe and striatal dysfunction, we propose that children with ADHD have dysfunction in a right-sided frontal-striatal system. Motor restlessness may reflect frontal lobe dysfunction due to impairment of the mesocortical dopamine system.

Clinical management of attention deficit hyperactivity disorder.

This article reviews current approaches to the diagnosis and management of children with attention deficit hyperactivity disorder in a multidisciplinary setting. The physician's role in terms of data collection, formulation of the diagnosis, and discussion of findings with the parents and child is reviewed. The use of psychostimulants in this condition is reviewed, and some case vignettes are presented.

Phonological awareness training and remediation of analytic decoding deficits in a group of severe dyslexics.

The goal of the present study was to evaluate the effectiveness of the Auditory Discrimination in Depth Program (ADD) in remediating the analytic decoding deficits of a group of severe dyslexics. A group of ten severely dyslexic students ranging in age from 93 to 154 months were treated in a clinic setting for 38 to 124 hours (average of 65 hours). Pre- and post-treatment testing was done with the Woodcock Reading Mastery Test and the Lindamood Auditory Conceptualization to assess changes in phonological awareness and analytic decoding skills. Results revealed statistically significant gains in phonological awareness and analytic decoding skills.

Facial affect recognition in children: a comparison of the performance of children with right and left hemisphere lesions.

This study tests the hypothesis that the right hemisphere is specialized for the processing of emotional information in children, as it is in adults. We compared the performance of eight children with right-hemisphere lesions and eight with left-hemisphere lesions on a test of facial affect recognition. The mean score of the right-hemisphere group fell significantly below that of the left-hemisphere group and normal controls, suggesting that the specialization of the right hemisphere occurs early in development. This finding is consistent with clinical observations that children with right-hemisphere dysfunction manifest a high incidence of difficulty in social interactions.

Attention deficit disorder in children: a neglect syndrome?

This study tests the hypothesis that children with attention deficit disorder (ADD) resemble adults with inattention and neglect secondary to right hemisphere dysfunction. A letter cancellation task was administered to seven boys with ADD and five controls. As a group, the subjects with ADD made significantly more overall errors of omission and left-sided errors than controls, suggesting that they resemble adults with right hemisphere dysfunction.

Computed tomography in neuronal ceroid lipofuscinosis: four case reports.

The computed tomography findings are discussed in four cases of neuronal ceroid lipofuscinosis. When this severely progressive inherited disease of lipid metabolism is suspected, confirmation may be obtained with electron microscopy of peripheral lymphocytes and certain tissues. Some physiologic-pathologic features are discussed.

Right-hemisphere deficit syndrome in children.

The author describes 15 children with behavioral disturbances, a characteristic neuropsychological profile, and neurological findings consistent with right-hemisphere damage or dysfunction. Almost all of the children had attention deficit disorder. Some were obtuse or unable to interpret social cues, others could not express their feelings but appeared to be sensitive and aware of the emotions of others. The older children were generally in psychotherapy or counseling but responded poorly, suggesting that a different approach to treatment may be indicated.